Arsenic-induced NFκB transactivation through Erks- and JNKs-dependent pathways in mouse epidermal JB6 cells

Tumor promoting effects of arsenic are believed to be associated with its transactivation activity on transcription factors, such as AP-1 and NFκB. However, the results from different groups studying the effects of arsenic on NFκB activation are contradictory in different cell models. Since arsenic is a strong skin carcinogen, we have investigated the activation of NFκB by arsenic in a mouse skin epidermal cell line, JB6 cells. Exposure of cells to arsenite or arsenate led to NFκB transactivation in mouse epidermal JB6 NFκB-luciferase reporter stable transfectants, C141 NFκB mass. This induction of NFκB activity by arsenic was dose- and time-dependent. The transactivation of NFκB by arsenic appeared to be through activation of Erks and JNKs pathways because increased NFκB activity by arsenic could be dramatically inhibited by either pre-treatment of cells with PD98059 or overexpression of dominant negative JNK₁. That Erks activation is required for arsenic-induced NFκB transactivation was further supported by the findings that arsenic-induced NFκB transactivation was impaired in JB6 30.7b cells, which were deficient in Erks.